Process for the preparation of 2-aryl-5- (perfluoro-alkyl) pyrrole compounds from N-[1-chloro-1-(perfluoroalkyl) methyl] arylimidoyl chloride compounds

ABSTRACT

There is provided a process for the preparation of 2-aryl-5-(perfluoroalkyl)pyrrole compounds from N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compounds. The 2-aryl-5-(perfluoroalkyl)pyrrole compounds are useful for the control of insect and acarid pests, and may also be used to prepare other pesticidal arylpyrrole compounds.  
     In addition, the present invention provides compounds which are useful as intermediates in the preparation of arylpyrrole compounds.

BACKGROUND OF THE INVENTION

[0001] 2-Aryl-5-(perfluoroalkyl)pyrrole compounds are useful asinsecticidal and acaricidal agents. In addition, those compounds arealso useful for the preparation of other insecticidal and acaricidalagents. In particular, 2-aryl-5-(perfluoroalkyl)pyrrole compounds arekey intermediates in the preparation of arylpyrrole compounds such aschlorfenapyr. Accordingly, there is an ongoing search to discover newmethods for the preparation of 2-aryl-5-(perfluoroalkyl)pyrrolecompounds.

[0002] U.S. Pat. No. 5,145,986 discloses that2-aryl-5-(trifluoromethyl)pyrrole compounds may be prepared by reactingan N-(substituted benzyl)-2,2,2-trifluoro-acetimidoyl chloride compoundwith an α-halo-α,β-unsaturated nitrile, ester or nitro compound in thepresence of a base. However, the process described in U.S. Pat. No.5,145,986 is not entirely satisfactory because the requiredα-halo-α,β-unsaturated nitrile, ester or nitro compound is prepared in atwo step—halogenation/dehydrohalogenation—process.

[0003] U.S. Pat. Nos. 5,446,170 and 5,426,225 disclose that2-aryl-5-(trifluoromethyl)pyrrole compounds may be obtained in severalsteps from the appropriate aldehyde. The processes described in U.S.Pat. Nos. 5,446,170 and 5,426,225 require the use of an aminonitrileintermediate which is obtained via the Strecker synthesis from theappropriate aldehyde. However, the use of the Strecker synthesis is notentirely satisfactory because of cyanide containing waste streams.

[0004] It is, therefore, an object of the present invention to provide anew process for the preparation of 2-aryl-5-(perfluoroalkyl)pyrrolecompounds which avoids the use of α-halo-α,β-unsaturated nitrile, esterand nitro compounds and the Strecker synthesis.

[0005] It is also an object of this invention to provide a new processfor the preparation of arylpyrrole compounds such as chlorfenapyr.

[0006] A further object of the present invention is to provide newintermediate compounds which are useful in the processes describedhereinbelow.

[0007] Those and other objects of the present invention will become moreapparent from the detailed description thereof set forth below.

SUMMARY OF THE INVENTION

[0008] The present invention provides a new process for the preparationof 2-aryl-5-(perfluoroalkyl)pyrrole compounds having the structuralformula I

[0009] wherein

[0010] W is hydrogen or C_(m)F_(2m+1);

[0011] Y is CN, NO₂ or CO₂R;

[0012] R is C₁-C₄alkyl;

[0013] m and n are each independently an integer of 1, 2, 3, 4, 5, 6, 7or 8;

[0014] A is

[0015] L is hydrogen or halogen;

[0016] M and Q are each independently hydrogen, halogen, CN, NO₂,C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄-sulfinyl,C₁-C₄haloalkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl orwhen M and Q are on adjacent positions they may be taken together withthe carbon atoms to which they are attached to form a ring in which MQrepresents the structure —OCH₂O—, —OCF₂O— or —CH═CH—CH═CH—;

[0017] R₁, R₂ and R₃ are each independently hydrogen, halogen, NO₂, CHOor R₂ and R₃ may be taken together with the atoms to which they areattached to form a ring in which R₂R₃ is represented by the structure

[0018] R₄R₅R₆ and R₇ are each independently hydrogen, halogen, CN orNO₂; and

[0019] X is O or S

[0020] which process comprises reacting anN-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compoundhaving the structural formula II

[0021] wherein A and n are as described above with a dieneophilecompound having the structural formula III

[0022] wherein W and Y are as described above and a base in the presenceof a solvent.

[0023] The present invention further provides novel compounds having thestructural formulas II, IV and V

[0024] wherein n and A are as described hereinabove.

DETAILED DESCRIPTION OF THE INVENTION

[0025] The process of the present invention preferably comprisesreacting an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloridecompound of formula II with at least about one molar equivalent,preferably about one to four molar equivalents, of a dienophile compoundof formula III and at least about one molar equivalent, preferably aboutone to four molar equivalents, of a base in the presence of a solventpreferably at a temperature range of about 5° C. to 100° C. to form2-aryl-5-(perfluoro-alkyl)pyrrole compounds of formula I.

[0026] Alternatively, the formula I compounds may be prepared by formingthe formula III dienophile compounds in situ. This process comprisesreacting an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloridecompound of formula II with preferably about one to four molarequivalents of a substituted haloethane compound having the structuralformula VI

[0027] wherein W and Y are as described hereinabove and Z is Cl, Br orI, and at least about two molar equivalents, preferably about two tofive molar equivalents, of a base in the presence of a solventpreferably at a temperature range of about 5° C. to 100° C. to form2-aryl-5-(perfluoro-alkyl)pyrrole compounds of formula I.

[0028] Advantageously, the present invention provides new processes forthe preparation of 2-aryl-5-(perfluoro-alkyl)pyrrole compounds whichavoid the use of α-halo-α,β-unsaturated nitrile, ester and nitrocompounds and the Strecker synthesis.

[0029] The formula I compounds of this invention may be isolated byconventional procedures such as dilution of the reaction mixture withwater and filtration or, alternatively, extraction with a suitablesolvent. Suitable extraction solvents include water-immiscible solventssuch as ether, ethyl acetate, toluene, methylene chloride and the like.

[0030] Bases suitable for use in this invention includetri-(C₁-C₆alkyl)amines such as trimethylamine, triethylamine,tripropylamine, tributylamine, diisopropylethylamine and the like;alkali metal carbonates such as potassium carbonate and sodiumcarbonate; alkali metal hydroxides such as potassium hydroxide andsodium hydroxide; alkali metal acetates such as potassium acetate andsodium acetate; and heterocyclic tertiary amines including, but notlimited to, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU);1,5-diaza-bicyclo[4.3.0]non-5-ene (DBN); 1,4-diazabicyclo[2.2.2]-octane;pyridine; substituted pyridines such as 2,6-dimethylpyridine,2-methylpyridine, 3-methylpyridine, 4-methylpyridine and the like;quinoline; and substituted quinolines. Preferred bases includetri-(C₁-C₆alkyl)amines, 1,8-diazabicyclo[5.4.0]undec-7-ene,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]-octane,potassium carbonate and sodium carbonate.

[0031] Solvents suitable for use in the present invention include, butare not limited to, carboxylic acid amides such asN,N-dimethylformamide, N,N-dimethylacetamide and the like; N-substitutedpyrrolidinones such as N-methyl-pyrrolidinone and the like; nitritessuch as aceto-nitrile, propionitrile and the like; halogenatedhydro-carbons such as methylene chloride, chloroform, carbontetrachloride and the like; ethers such as tetrahydro-furan, dioxane andthe like; sulfoxides such as dimethyl sulfoxide and the like; andmixtures thereof. Preferred solvents include carboxylic acid amides andnitrites and mixtures thereof. N,N-dimethylformamide and acetonitrileand mixtures thereof are especially preferred for use in the presentinvention.

[0032] Exemplary of halogen hereinabove are fluorine, chlorine, bromineand iodine. The terms “C₁,-C₄haloalkyl”, “C₁-C₄haloalkoxy”,“C₁-C₄haloalkylthio”, “₁-C₁-C₄haloalkylsulfinyl” and“C₁-C₄haloalkylsulfonyl” are defined as a C₁-C₄alkyl, C₁-C₄alkoxy,C₁-C₄alkylthio, C₁-C₄alkylsulfinyl or C₁-C₄alkylsulfonyl groupsubstituted with one or more halogen atoms, respectively.

[0033] The present invention is especially useful for the preparation offormula I compounds wherein

[0034] W is hydrogen;

[0035] Y is CN;

[0036] n is 1 or 2;

[0037] A is

[0038] L is hydrogen or halogen; and

[0039] M and Q are each independently hydrogen, halogen, C₁-C₄haloalkylor C₁-C₄haloalkoxy.

[0040] In particular, the present invention is useful for thepreparation of

[0041] 2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile;

[0042] 2-(p-bromophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile;

[0043] 2-(3,5-dichlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile;

[0044]2-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile; and

[0045]2-[4-(trifluoromethyl)phenyl]-5-(trifluoromethyl)pyrrole-3-carbonitrile,among others.

[0046] The present invention also relates toN-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compoundshaving the structural formula II

[0047] wherein

[0048] n is an integer of 1, 2, 3, 4, 5, 6, 7 or 8;

[0049] A is

[0050] L is hydrogen or halogen;

[0051] M and Q are each independently hydrogen, halogen, CN, NO₂,C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfinyl,C₁-C₄haloalkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl orwhen M and Q are on adjacent positions they may be taken together withthe carbon atoms to which they are attached to form a ring in which MQrepresents the structure —OCH₂O—, —OCF₂O— or —CH═CH—CH═CH—;

[0052] R₁, R₂ and R₃ are each independently hydrogen, halogen, NO₂, CHOor R₂ and R₃ may be taken together with the atoms to which they areattached to form a ring in which R₂R₃ is represented by the structure

[0053] R₄, R₅, R₆ and R₇ are each independently hydrogen, halogen, CN orNO₂; and

[0054] X is O or S.

[0055] Preferred formula II compounds of this invention are thosewherein

[0056] n is 1 or 2;

[0057] A is

[0058] L is hydrogen or halogen; and

[0059] M and Q are each independently halogen, C₁-C₄haloalkyl orC₁-C₄haloalkoxy.

[0060] Formula II compounds which are particularly useful in theprocesses of this invention include

[0061] N-[1-chloro-(2,2,2-trifluoroethyl)]-4-chlorobenzimidoyl chloride;

[0062] N-[1-chloro-(2,2,2-trifluoroethyl)]-4-bromobenzimidoyl chloride;

[0063] N-[1-chloro-(2,2,2-trifluoroethyl)]-3,5-dichlorobenz-imidoylchloride;

[0064] N-[1-chloro-(2,2,2-trifluoroethyl)]-3,4,5-trichlorobenzimidoylchloride; and

[0065]N-[1-chloro-(2,2,2-trifluoroethyl)]-4-(trifluoromethyl)benzimidoylchloride, among others.

[0066] Starting N-[1-chloro-1-(perfluoroalkyl)methyl]-arylimidoylchloride compounds of formula II may be prepared, as shown in FlowDiagram I, by reacting an arylamide compound having the structuralformula VII with a (perfluoroalkyl)aldehyde C₁-C₆alkyl hemiacetalcompound having the structural formula VIII to form anN-[1-hydroxy-1-(perfluoroalkyl)methyl]arylamide compound having thestructural formula IV, and reacting the formula IV compound withphosphorus pentachloride.

Flow Diagram I

[0067] Alternatively, N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoylchloride compounds of formula II may be prepared, as shown in FlowDiagram II, by reacting anN-[1-hydroxy-1-(perfluoroalkyl)methyl]arylamide of formula IV withphosphorus trichloride to form anN-[1-chloro-l-(perfluoroalkyl)methyl]arylamide compound having thestructural formula V, and reacting the formula V compound withphosphorus pentachloride.

Flow Diagram II

[0068]

[0069] The present invention also relates to the formula IV and Vcompounds which are used to prepare the formula II compounds. Inparticular, the present invention providesN-[1-hydroxy-1-(perfluoroalkyl)methyl]arylamide compounds having thestructural formula IV and N-[1-chloro-1-(perfluoroalkyl)methyl]arylamidecompounds having the structural formula V

[0070] wherein

[0071] n is an integer of 1, 2, 3, 4, 5, 6, 7 or 8;

[0072] A is

[0073] L is hydrogen or halogen;

[0074] M and Q are each independently hydrogen, halogen, CN, NO₂,C₁-C₄alkyl, C₁-C₄haloalkyl, C₁₋C₄ alkoxy, C₁-C₄haloalkoxy,C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfinyl,C₁-C₄haloalkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl orwhen M and Q are on adjacent positions they may be taken together withthe carbon atoms to which they are attached to form a ring in which MQrepresents the structure —OCH₂O—, —OCF₂O— or —CH═CH—CH═CH—;

[0075] R₂, R₂ and R₃ are each independently hydrogen, halogen, NO₂, CHOor R₂ and R₃ may be taken together with the atoms to which they areattached to form a ring in which R₂R₃ is represented by the structure

[0076] R₄, R₅, R₆ and R₇ are each independently hydrogen, halogen, CN orNO₂; and

[0077] X is O or S.

[0078] Preferred formula IV and V compounds of this invention are thosewherein

[0079] n is 1 or 2;

[0080] A is

[0081] L is hydrogen or halogen; and

[0082] M and Q are each independently halogen, C₁-C₄haloalkyl orC₁-C₄haloalkoxy.

[0083] Formula IV compounds which are particularly useful for thepreparation of arylpyrrole compounds include

[0084] N-(1-hydroxy-2,2,2-trifluoroethyl)-4-chorobenzamide;

[0085] N-(1-hydroxy-2,2,2-trifluoroethyl)-4-bromobenzamide;

[0086] N-(1-hydroxy-2,2,2-trifluoroethyl)-3,5-dichlorobenzamide;

[0087] N-(1-hydroxy-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzamide; and

[0088] N-(1-hydroxy-2,2,2-trifluoroethyl)-4-(trifluoromethyl)benzamide,among others.

[0089] Formula V compounds which are particularly useful for thepreparation of arylpyrrole compounds include

[0090] N-(1-chloro-2,2,2-trifluoroethyl)-4-chlorobenzamide;

[0091] N-(1-chloro-2,2,2-trifluoroethyl)-4-bromobenzamide;

[0092] N-(1-chloro-2,2,2-trifluoroethyl)-3,5-dichlorobenzamide;

[0093] N-(1-chloro-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzamide; and

[0094] N-(1-chloro-2,2,2-trifluoroethyl)-4-(trifluoromethyl)benzamide,among others.

[0095] The formula I compounds are useful for the control of insect andacarid pests. In addition, the formula I compounds may be used toprepare other arylpyrrole insecticidal and acaricidal agents having thestructural formula IX

[0096] wherein

[0097] Y is CN, NO₂ or CO₂R;

[0098] R is C₁-C₄alkyl;

[0099] n is an integer of 1, 2, 3, 4, 5, 6, 7 or 8;

[0100] A is

[0101] L is hydrogen or halogen;

[0102] M and Q are each independently hydrogen, halogen, CN, NO₂,C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfinyl,C₁-C₄haloalkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl orwhen M and Q are on adjacent positions they may be taken together withthe carbon atoms to which they are attached to form a ring in which MQrepresents the structure—OCH₂O—, —OCF₂O— or —CH═CH—CH═CH—;

[0103] R₁, R₂ and R₃ are each independently hydrogen, halogen, NO₂, CHOor R₂ and R₃ may be taken together with the atoms to which they areattached to form a ring in which R₂R₃ is represented by the structure

[0104] R₄, R₅, R₆ and R₇ are each independently hydrogen, halogen, CN orNO₂;

[0105] X is O or S;

[0106] Hal is a halogen atom; and

[0107] J is hydrogen or C₁-C₆alkoxymethyl.

[0108] The present invention is especially useful for the preparation ofarylpyrrole compounds of formula IX wherein

[0109] Y is CN;

[0110] n is 1 or 2;

[0111] A is

[0112] L is hydrogen or halogen;

[0113] M and Q are each independently hydrogen, halogen, C₁-C₄haloalkylor C₁-C₄haloalkoxy;

[0114] Hal is Br or Cl; and

[0115] J is hydrogen or ethoxymethyl.

[0116] In particular, the present invention is useful for thepreparation of formula IX arylpyrrole compounds such as

[0117]4-bromo-2-(p-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile,(chlorfenapyr);

[0118]4-bromo-2-(3,5-dichlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile;

[0119]4-bromo-2-(3,5-dichlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile;and

[0120]4-bromo-2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile,among others.

[0121] Advantageously, formula IX arylpyrrole compounds may be preparedby a process which comprises:

[0122] (a) reacting an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoylchloride compound of formula II with a dienophile compound having thestructural formula X

[0123] wherein Y is as described above and a base in the presence of asolvent to form a 2-aryl-5-(perfluoro-alkyl)pyrrole compound having thestructural formula XI

[0124] (b) halogenating the formula XI compound to form the arylpyrrolecompound of formula IX wherein J is hydrogen; and

[0125] (c) optionally alkoxymethylating the formula IX compound whereinJ is hydrogen to form the formula IX arylpyrrole compound wherein J isC₁-C₆ alkoxymethyl.

[0126] Alternatively, arylpyrrole compounds of formula IX may beprepared by a process which comprises:

[0127] (a) reacting an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoylchloride compound of formula II with a substituted haloethane compoundhaving the structural formula XII

[0128] wherein Y is as described above and Z is Cl, Br or I, and atleast about two molar equivalents of a base in the presence of a solventto form a 2-aryl-5-(perfluoro-alkyl)pyrrole compound having thestructural formula XI

[0129] (b) halogenating the formula XI compound to form the arylpyrrolecompound of formula IX wherein J is hydrogen; and

[0130] (c) optionally alkoxymethylating the formula IX compound whereinJ is hydrogen to form the formula IX arylpyrrole compound wherein J isC₁-C₆alkoxymethyl.

[0131] Halogenation methods may be any known methods such as thosedescribed in U.S. Pat. Nos. 5,010,098 and 5,449,789.

[0132] Alkoxymethylation procedures suitable for use in this inventioninclude conventional procedures known in the art (see, e.g., U.S. Pat.Nos. 5,010,098 and 5,359,090). In a preferred embodiment of thisinvention, the alkoxymethylation procedure comprises reacting a formulaIX compound wherein J is hydrogen with a di-(C₁-C₆alkoxy)methanecompound, N,N-dimethylformamide and phosphorous oxychloride in thepresence of an aprotic solvent to form a reaction mixture and treatingthe reaction mixture with a tertiary amine.

[0133] In order to facilitate a further understanding of this invention,the following examples are presented primarily for the purpose ofillustrating more specific details thereof. The scope of the inventionshould not be deemed limited by the examples, but encompasses the entiresubject matter defined in the claims.

EXAMPLE 1 Preparation ofN-(1-Hydroxy-2,2,2-trifluoroethyl)-4-chlorobenzamide

[0134]

[0135] A solution of 4-chlorobenzamide (22.0 g, 0.141 mol) andtrifluoroacetaldehyde ethyl hemiacetal (25.0 g as is, 22.5 g real, 0.156mol) in dioxane (200 mL) is treated with anhydrous sodium sulfate (10 g,to dry the 10% water in the hemiacetal) and refluxed for 60 hours. Thesolids are filtered and the filtrate is evaporated to a solid. Thesolids are dissolved in about 200 mL of 15% ethyl acetate in heptane.Unreacted starting material (5.6 g) crystallizes out and is filtered.The title product is obtained from the mother liquors as a whitecrystalline solid (22.1 g, 82.9% based on recovery of startingmaterial): mp 139.5-140.5° C.; characterized by ¹H and ¹⁹F NMR and Massspectra. ¹H NMR (DMSO-d₆) δ9.45 (d, J=8.7 Hz, NH), 7.93, 7.54 ( AB withfine splitting, J=8.4 Hz, ArH), 7.54 (broad s, OH), 5.90 (m, J=8.7, 2.9,5.8 Hz, CH); ¹⁹F NMR δ-80.3 (d, J=5 Hz).

[0136] Following essentially the same procedure, but using theappropriately substituted benzamide, the following compounds areobtained:

L M Q mp ° C. Cl H Cl 152.5-153   H Br H   148-148.5 H CF₃ H   124-124.5

EXAMPLE 2 Preparation ofN-[1-Chloro-(2,2,2-trifluoroethyl)]-4-chlorobenzimidoyl chloride

[0137] Method A

[0138] A mixture of N-(1-hydroxy-2, 2,2-trifluoroethyl)-4-chlorobenzamide (22.1 g, 0.087 mol) in phosphorusoxychioride (8 mL) is treated with phosphorus pentachioride (40.0 g,0.192 mol), heated to and held at 100° C. for 15-20 minutes, cooled, andconcentrated in vacuo to obtain a residue. The residue is distilled togive the title product as a clear liquid (22.2 g, 87.8% yield): bp77-78° C. (0.1 mm); characterized by IR, ¹H and ¹⁹F NMR, and Massspectra. ¹H NMR (CDCl₃) δ8.06, 7.44 ( d with fine splitting, J=8.9 Hz,ArH), 5.92 (q, J=4.9 Hz, CH); ¹⁹F NMRδ-77.9 (d, J=5 Hz).

Method B

[0139]

[0140] A mixture of N-(1-hydroxy-2,2,2-trifluoroethyl)-4-chlorobenzamide(16.3 g, 0.064 mol) in phosphorus oxychloride (10 mL) is treated withphosphorus trichloride (9.3 g, 0.675 mol) and heated to and held at 80°C. for 15-20 minutes. ¹⁹F NMR shows clean and complete conversion toN-(1-chloro-2,2,2-trifluoroethyl)-4-chlorobenzamide. The reactionmixture is then cooled to room temperature, treated with phosphoruspentachloride (28.0 g, 0.135 mol), and heated to and held at 100° C. for1 hour. The phosphorus oxychloride is then removed in vacuo and theresultant residue is vacuum distilled to give the title product as aclear liquid (18.5 g, 100% yield): bp 94-96° C. (0.5 mm).

[0141] Following essentially the same procedure as described in MethodA, but using the appropriately substitutedN-(1-hydroxy-2,2,2-trifluoroethyl)-4-benzamide, the following compoundsare obtained:

L M Q bp Cl H Cl 114° C. (0.3 mm) H Br H 95-96° C. (0.07 mm) H CF₃ Hwaxy solid

EXAMPLE 3 Preparation of2-(p-Chlorophenyl)-5-(trifluoro-methyl)pyrrole-3-carbonitrile

[0142]

[0143] A solution ofN-[1-chloro-(2,2,2-trifluoroethyl)]-4-chlorobenzimidoyl chloride (5.80g, 0.02 mol) and acrylonitrile (1.33 g, 0.025 mol) inN,N-dimethyl-formamide (15 mL) is treated with1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 8.53 g, 0.056 mol) over 1 hourwhile maintaining the temperature at 45°-50° C. The reaction mixture isthen stirred at 50° C. for 4 hours, quenched with dilute HCl, andextracted with ethyl acetate. The organic extract is concentrated invacuo to obtain a residue. Flash chromatography of the residue on silicagel, packed and eluted with 20% ethyl acetate in heptane, andcrystallization from heptane and small amount of ethyl acetate gives thetitle product as a white crystalline solid (2.1 g, 38.9% yield): mp239-240° C. (dec).

[0144] Following essentially the same procedure, but using theappropriately substituted N-[1-chloro-(2,2,2-trifluoroethyl)]benzimidoylchloride, the following compounds are obtained:

L M Q mp ° C. Cl H Cl 236.5-237   H Br H 248-249 H CF₃ H 216.5-218.5

EXAMPLE 4 Preparation of Methyl2-(4-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carboxylate

[0145]

[0146] A solution ofN-[1-chloro-(2,2,2-trifluoroethyl)]-4-chlorobenzimidoyl chloride (3.40g, 0.012 mol) and methyl acrylate (1.26 g, 0.015 mol) inN,N-dimethylformamide (10 mL) is treated with1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 5.0 g, 0.033 mol) over 1 hour.The reaction mixture is then held at 60° C. for 15 minutes, quenchedwith dilute HCl, and extracted with ethyl acetate. The organic extractis concentrated in vacuo to obtain a residue. Flash chromatography ofthe residue on silica gel, packed and eluted with 20% ethyl acetate inheptane, and crystallization from heptane gives the title product as ayellow solid (0.95 g, 26.0% yield) which is identified by ₁H and ¹⁹F NMRspectral analyses.

EXAMPLE 5 Preparation of4-Bromo-2-(4-chlorophenyl)-5-(tri-fluoromethyl)pyrrole-3-carbonitrile

[0147]

[0148] A solution ofN-[1-chloro-(2,2,2-trifluoroethyl)]-4-chlorobenzimidoyl chloride (5.80g, 0.02 mol) and acrylonitrile (1.33 g, 0.025 mol) inN,N-dimethyl-formamide (15 mL) under a nitrogen atmosphere is treatedwith N,N-diisopropylethylamine (DIPEA, 7.8 g, 0.06 mol) over 30 minutes,heated to and held at 45-47° C. for 18 hours, cooled to roomtemperature, treated with bromine (3.2 g, 0.02 mol), stirred at roomtemperature for 1 hour, quenched with water, and extracted with ethylacetate. The organic extract is concentrated in vacuo to obtain aresidue. Flash column chromatography of the residue on silica gel,packed with 15% ethyl acetate in heptane and eluted with 20% ethylacetate in heptane, gives the title product as white solid (1.6 g, 22.9%yield) which is identified by ¹H and ¹⁹F NMR spectral analyses.

EXAMPLE 6 Preparation ofN-(1-Chloro-2,2,2-trifluoro-ethyl)-4-chlorobenzamide

[0149]

[0150] A mixture of N-(1-hydroxy-2,2,2-trifluoroethyl)-4-chlorobenzamide(2.53 g, 0.01 mol) in phosphorus oxychloride (2 mL) is treated withphosphorus trichloride (1.57 g, 0.012 mol), heated to and held at 80° C.for 30 minutes, and concentrated in vacuo to obtain a residue. Theresidue is dissolved in hot heptane, decanted from the waxy phosphorusproducts, and crystallized to give the title product as a whitecrystalline solid (2.43 g, 89.3% yield): mp 119.0-121.0° C.; IR (Nujol)3266, 1668 cm⁻¹; ¹H NMR (CDCl₃) δ7.76 and 7.46 (AB with fine splitting,ArH), 6.86 (d, J=8.5 Hz, NH, moves to 10.24 in DMSO-d₆), 6.55(m, CH);¹⁹F NMRδ-77.7(d, J=5 Hz).

[0151] Following essentially the same procedure, but using theappropriately substituted N-(1-hydroxy-2,2,2-trifluoroethyl)benzamide,the following compounds are obtained:

L M Q mp ° C. Cl H Cl 163.5-164   H Br H   135-136.5 H CF₃ H 122.5-123.5

I claim:
 1. A process for the preparation of a2-aryl-5-(perfluoroalkyl)pyrrole compound having the formula I

wherein W is hydrogen or C_(m)F_(2m+1); Y is CN, NO₂ or CO₂R; R isC₁-C₄alkyl; m and n are each independently an integer of 1, 2, 3, 4, 5,6, 7 or 8; A is

L is hydrogen or halogen; M and Q are each independently hydrogen,halogen, CN, NO₂, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy,C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfinyl,C₁-C₄haloalkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl orwhen M and Q are on adjacent positions they may be taken together withthe carbon atoms to which they are attached to form a ring in which MQrepresents the structure —OCH₂O—, —OCF₂O— or —CH═CH—CH═CH—; R₁, R₂ andR₃ are each independently hydrogen, halogen, NO₂,CHO or R₂ and R₃ may betaken together with the atoms to which they are attached to form a ringin which R₂R₃ is represented by the structure

R₄, R₅, R6 and R₇ are each independently hydrogen, halogen, CN or NO₂;and X is O or S, which process comprises reacting anN-[₁-chloro-₁-(perfluoroalkyl)methyl]arylimidoyl chloride compoundhaving the structural formula II

wherein A and n are as described above with a dieneophile compoundhaving the structural formula III or a substituted haloethane compoundhaving the structural formula VI

wherein W and Y are as described above and Z is Cl, Br or I, and a basein the presence of a solvent.
 2. The process according to claim 1wherein the base is selected from the group consisting of atri-(C₁-C₆(C₁-C₆alkyl)amine, an alkali metal carbonate and aheterocyclic tertiary amine.
 3. The process according to claim 2 whereinthe base is selected from the group consisting of atri-(C₁-C₆alkyl)amine, 1,8-diazabicyclo[5.4.0]undec-7-ene,1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane,potassium carbonate and sodium carbonate.
 4. The process according toclaim 3 wherein the tri-(C₁-C₆alkyl)amine is selected from the groupconsisting of trimethylamine, triethylamine, tripropylamine,tributylamine and diisopropylethylamine.
 5. The process according toclaim 1 wherein the solvent is selected from the group consisting of acarboxylic acid amide and a nitrile and mixtures thereof.
 6. The processaccording to claim 5 wherein the solvent is selected from the groupconsisting of N,N-dimethylformamide and acetonitrile and mixturesthereof.
 7. The process according to claim 1 wherein the dieneophile ispresent in the amount of about one to four molar equivalents and thebase is present in the amount of about one to four molar equivalents. 8.The process according to claim 1 wherein the substituted haloethanecompound is present in the amount of about one to four molar equivalentsand the base is present in the amount of about two to five molarequivalents.
 9. The process according to claim 1 wherein W is hydrogen;Y is CN; n is 1 or 2; A is

L is hydrogen or halogen; and M and Q are each independently hydrogen,halogen, C₁-C₄haloalkyl or C₁-C₄haloalkoxy.
 10. A process for thepreparation of an arylpyrrole compound having the structural formula IX

wherein Y is CN, NO₂ or CO₂R; R is C₁-C₄alkyl; n is an integer of 1, 2,3, 4, 5, 6, 7 or 8; A is

L is hydrogen or halogen; M and Q are each independently hydrogen,halogen, CN, NO₂, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy,C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfinyl,C₁-C₄haloalkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl orwhen M and Q are on adjacent positions they may be taken together withthe carbon atoms to which they are attached to form a ring in which MQrepresents the structure —OCH₂O—, —OCF₂O— or —CH═CH—CH═CH—; R₁, R₂ andR₃ are each independently hydrogen, halogen, NO₂, CHO or R₂ and R₃ maybe taken together with the atoms to which they are attached to form aring in which R₂R₃ is represented by the structure

R₄, R₅, R₆ and R₇ are each independently hydrogen, halogen, CN or NO₂; Xis O or S; Hal is a halogen atom; and J is hydrogen orC₁-C₆alkoxymethyl, which process comprises the steps of: (a) reacting anN-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compoundhaving the structural formula II

 wherein A and n are as described above with a dieneophile compoundhaving the structural formula X or a substituted haloethane compoundhaving the structural formula XII

 wherein Y is as described above and Z is Cl, Br or I, and a base in thepresence of a solvent to form a 2-aryl-5-(perfluoroalkyl)pyrrolecompound having the structural formula XI

(b) halogenating the formula XI compound to form the arylpyrrolecompound of formula IX wherein J is hydrogen; and (c) optionallyalkoxymethylating the formula IX compound wherein J is hydrogen.
 11. Theprocess according to claim 10 wherein step (c) comprises reacting theformula IX compound wherein J is hydrogen with a di-(C₁-C₆alkoxy)methanecompound, N,N-dimethylformamide and phosphorous oxychloride in thepresence of an aprotic solvent to form a reaction mixture and treatingthe reaction mixture with a tertiary amine.
 12. A compound having thestructural formula II, IV or V

wherein n is an integer of 1, 2, 3, 4, 5, 6, 7 or 8; A is

L is hydrogen or halogen; M and Q are each independently hydrogen,halogen, CN, NO₂, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy,C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfinyl,C₁-C₄haloalkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl orwhen M and Q are on adjacent positions they may be taken together withthe carbon atoms to which they are attached to form a ring in which MQrepresents the structure —OCH₂O—, —OCF₂O— or —CH═CH—CH═CH—; R₁, R₂ andR₃ are each independently hydrogen, halogen, NO₂, CHO or R₂ and R₃ maybe taken together with the atoms to which they are attached to form aring in which R₂R₃ is represented by the structure

R₄, R₅, R₆ and R₇ are each independently hydrogen, halogen, CN or NO₂;and X is O or S.
 13. The compound according to claim 12 wherein n is 1or 2; A is

L is hydrogen or halogen; and M and Q are each independently hydrogen,halogen, C₁-C₄haloalkyl or C₁-C₄haloalkoxy.
 14. The compound accordingto claim 12 selected from the group consisting ofN-[1-chloro-(2,2,2-trifluoroethyl)]-4-chlorobenzimidoyl chloride;N-[1-chloro-(2,2,2-trifluoroethyl)]-4-bromobenzimidoyl chloride;N-[1-chloro-(2,2,2-trifluoroethyl)]-3,5-dichlorobenzimidoyl chloride;N-[1-chloro-(2,2,2-trifluoroethyl)]-3,4,5-trichlorobenzimidoyl chloride;and N-[1-chloro-(2,2,2-trifluoroethyl)]-4-(trifluoromethyl)benzimidoylchloride.
 15. The compound according to claim 12 selected from the groupconsisting of N-(1-hydroxy-2,2,2-trifluoroethyl)-4-chlorobenzamide;N-(1-hydroxy-2,2,2-trifluoroethyl)-4-bromobenzamide;N-(1-hydroxy-2,2,2-trifluoroethyl)-3,5-dichlorobenzamide;N-(1-hydroxy-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzamide; andN-(1-hydroxy-2,2,2-trifluoroethyl)-4-(trifluoromethyl)benzamide.
 16. Thecompound according to claim 12 selected from the group consisting ofN-(1-chloro-2,2,2-trifluoroethyl)-4-chlorobenzamide;N-(1-chloro-2,2,2-trifluoroethyl)-4-bromobenzamide;N-(1-chloro-2,2,2-trifluoroethyl)-3,5-dichlorobenzamide;N-(1-chloro-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzamide; andN-(1-chloro-2,2,2-trifluoroethyl)-4-(trifluoromethyl)benzamide.
 17. Aprocess for the preparation of anN-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoyl chloride compoundhaving the structural formula II

wherein n is an integer of 1, 2, 3, 4, 5, 6, 7 or 8; A is

L is hydrogen or halogen; M and Q are each independently hydrogen,halogen, CN, NO₂, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy,C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfinyl,C₁-C₄haloalkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl orwhen M and Q are on adjacent positions they may be taken together withthe carbon atoms to which they are attached to form a ring in which MQrepresents the structure —OCH₂O—, —OCF₂O— or —CH═CH—CH═CH—; R₁, R₂ andR₃ are each independently hydrogen, halogen, NO₂, CHO or R₂ and R₃ maybe taken together with the atoms to which they are attached to form aring in which R₂R₃ is represented by the structure

R₄, R₅, R₆and R₇ are each independently hydrogen, halogen, CN or NO₂;and X is O or S, which process comprises reacting anN-[₁-hydroxy-1-(perfluoroalkyl)methyl]arylamide compound having thestructural formula IV

wherein n and A are as described above with phosphorus pentachloride.18. The process according to claim 17 wherein n is 1 or 2; A is

L is hydrogen or halogen; and M and Q are each independently hydrogen,halogen, C₁-C₄haloalkyl or C₁-C₄haloalkoxy.
 19. A process for thepreparation of an N-[1-chloro-1-(perfluoroalkyl)methyl]arylimidoylchloride compound having the structural formula II

wherein n is an integer of 1, 2, 3, 4, 5, 6, 7 or 8; A is

L is hydrogen or halogen; M and Q are each independently hydrogen,halogen, CN, NO₂, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy,C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkylsulfinyl,C₁-C₄haloalkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl orwhen M and Q are on adjacent positions they may be taken together withthe carbon atoms to which they are attached to form a ring in which MQrepresents the structure —OCH₂O—, —OCF₂O— or —CH═CH—CH═CH—; R₁, R₂ andR₃ are each independently hydrogen, halogen, NO₂, CHO or R₂ and R₃ maybe taken together with the atoms to which they are attached to form aring in which R₂R₃ is represented by the structure

R₄, R₅, R₆ and R₇ are each independently hydrogen, halogen, CN or NO₂;and X is O or S, which process comprises reacting anN-[1-chloro-1-(perfluoroalkyl)methyl]arylamide compound having thestructural formula V

wherein n and A are as described above with phosphorus pentachloride.20. The process according to claim 19 wherein n is 1 or 2; A is

L is hydrogen or halogen; and M and Q are each independently hydrogen,halogen, C₁-C₄haloalkyl or C₁-C₄haloalkoxy.